Keywords
atropine
scopolamine
platyphylline
naloxone
pain sensitivity
hot plate test
mice
Abstract
Centrally acting M-cholinoreceptor antagonists are usually described as drugs that affect autonomic functions. However, their possible analgesic properties are still not well studied, even though tropane alkaloids were historically used for pain relief. Modern publications show contradictory results about the effect of atropine and scopolamine on pain sensitivity, and some authors discuss the role of cholinergic and opioid mechanisms in their antinociceptive action.
The aim of the study – to determine the effect of atropine sulfate, scopolamine hydrobromide, and platyphylline hydrotartrate over a wide range of doses, as well as naloxone, on pain sensitivity in mice in the hot plate test; and to identify the type of interaction between antagonists of M-cholinoreceptors and opioid receptors in their influence on nociception. The study used 117 adult male outbred white mice. In the hot plate test at 53 °C, the latency of the nociceptive reaction was measured (licking of the hind paw and other behavioral patterns such as jumps, licking of the front paws, and vertical standing) 30 min after drug administration. In the first series, the effect of scopolamine hydrobromide trihydrate (1.5 mg/kg, intraperitoneally) was evaluated. In the second series, atropine sulfate (0.1, 1, 5 mg/kg), platyphylline hydrotartrate (0.125 mg/kg and 1.25 mg/kg, equimolar to 0.1 and 1 mg/kg of atropine sulfate), scopolamine hydrobromide trihydrate (0.1 mg/kg and 1 mg/kg), and naloxone (5 mg/kg) were used alone and in combination with scopolamine (1 mg/kg). The instability of additional behavioral patterns confirmed that hind-paw licking is the most reliable nociceptive marker under the action of M-cholinoblockers. All studied M-cholinoblockers were able to reduce pain sensitivity. Atropine sulfate showed a dose-dependent effect: from a slight increase of latency at low doses to a strong and statistically significant analgesia at 5 mg/kg. Scopolamine and platyphylline showed strong analgesic effects already at low doses (0.1–0.125 mg/kg). Naloxone (5 mg/kg) produced a moderate but statistically significant antinociceptive effect. When naloxone was combined with scopolamine, the latency time more than doubled compared to baseline, showing a strong enhancement of effects and a complex interaction between cholinergic and opioid systems. The results show that M-cholinoblockers may have potential as adjuvant analgesics and highlight the importance of studying their interaction with the opioid system. This may help in developing new combined pharmacological approaches for pain treatment.
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